Leaky blood vessels that lose their ability to protect the spinal cord from toxins may
play a role in the development of amyotrophic lateral sclerosis, better known as ALS or
Lou Gehrig's disease, according to research published in the April issue of Nature
Neuroscience.

Researchers from the University of Pennsylvania School of Medicine are developing a novel
approach to screen for drugs to combat neurodegenerative diseases such as amyotrophic
lateral sclerosis, or Lou Gehrig's disease, using yeast cells.

Researchers at Southern Methodist University (SMU) and The University of Texas at Dallas
(UTD) have identified a group of chemical compounds that slow the degeneration of neurons,
a condition behind old-age diseases like Alzheimer's, Parkinson's and amyotrophic lateral
sclerosis (ALS). Their findings are featured in the November 2008 edition of Experimental
Biology and Medicine. SMU Chemistry Professor Edward R. Biehl and UTD Biology Professor
Santosh D'Mello teamed to test 45 chemical compounds. Four were found to be the most
potent protectors of neurons, the cells that are core components of the human brain,
spinal cord and peripheral nerves.The most common cause of neurodegenerative disease is
aging. Current medications only alleviate the symptoms but do not affect the underlying
cause  degeneration of neurons. The identification of compounds that inhibit
neuronal death is of urgent and critical importance.

The blood-spinal cord barrier is functionally impaired in areas of motor neuron damage in
mice modeling amyotrophic lateral sclerosis, report researchers at the University of South
Florida Center for Aging and Brain Repair. The barrier disruption was found in mice at
both early and late stages of ALS, a progressive neurodegenerative disease affecting nerve
cells in the brain and the spinal cord. The study appears in the online, open-access
journal PLoS ONE.

Gene newly linked to inherited ALS
may also play role in common dementia

Scientists at Washington University School of Medicine in St. Louis have linked a mutation
in a gene known as TDP-43 to an inherited form of amyotrophic lateral sclerosis, the
neurodegenerative condition often called Lou Gehrig's disease.

Researchers have provided a big new clue to help combat amyotrophic lateral sclerosis
(ALS), deciphering that the dense protein aggregates that contribute to the nerve decay of
ALS are composed of just one protein: superoxide dismutase (SOD1).

The national average of those who suffer from ALS is a mere .0005 percent. But  sit
down for this one  among those who reported suffering from drug induced
ALS, nearly a third were using cholesterol lowering drugs! Apparently, this class of
drugs can tangle a protein known as tau proteins.

Sustaining hope in the face of a chronic, debilitating illness such as amyotrophic lateral
sclerosis should be a goal of palliative care and can take many forms, representing a
continuum from focusing on the self to concern for others, as described in a paper
published in the April issue of Journal of Palliative Medicine, a peer-reviewed
publication of Mary Ann Liebert, Inc.

Caffeine Appears To Be Beneficial
In MalesBut Not FemalesWith Lou Gehrigs Disease

Amyotrophic lateral sclerosis (ALS) is a fatal disease that damages key neurons in the
brain and spinal cord. The disease causes progressive paralysis of voluntary muscles and
often death within five years of symptoms. Although ALS (Lou Gehrigs disease) was
discovered over a century ago, neither the cause nor a cure have been found, but several
mechanisms seem to play a role in its development, including oxidative stress. Researchers
agree that ALS is a multifactorial disease that involves a complex interplay between a
genetic predisposition and environmental factors. One environmental factor is diet. With
oxidative stress (which damages the cells) a common concern in ALS pathology, it is worth
examining what role antioxidants (which confer benefits to the cells) might play.
Antioxidants (the vitamins and nutrients that protect the cells from damage) are found in
commonly consumed beverages and foods. Coffee in particular has received attention as a
potent dietary antioxidant. It is worth noting that coffee has significantly more
antioxidant capacity than cocoa and green, black or herbal teas. However, coffee contains
several components, the largest of which are caffeine and chlorogenic acid, a dietary
polyphenol that is beneficial to the immune system. Previous studies have shown positive
effects with coffee, caffeine, or chlorogenic acid supplementation in improving oxidative
stress and its associated cell death mechanisms.

High levels of certain proteins in the spinal fluid could signal the onset of Lou Gehrig's
disease, according to researchers. The discovery of these biomarkers may lead to
diagnostic kits for early diagnosis, accurately measuring the progression of the disease
and monitoring the effects of treatment. Lou Gehrig's disease -- or Amyotrophic Lateral
Sclerosis (ALS) -- is caused by the degeneration of nerve cells controlling the voluntary
movement of muscles. However, it is hard to diagnose because symptoms such as muscle
weakness are common in other ailments and currently, there is no diagnostic test for the
disease. "The disease has to progress far enough so that the patient begins to
experience significant muscle weakness, so that a physician can identify the
problem," said James Connor, distinguished professor and vice-chair of neurosurgery,
Penn State Hershey. "If we had a biomarker we could start treatments earlier and
perhaps save more nerve cells and slow the disease." The problem is compounded by the
speed at which the disease progresses. In some patients the disease can run its course in
just a couple of years, while in others it can take seven to ten years. To find an early
warning signal for the onset of Lou Gehrig's disease, Connor and his colleagues, Zachary
Simmons and Ryan Mitchell at the Hershey Medical Center, focused their attention on
proteins related to inflammation in the spinal cord. Studies show that the progression of
the disease involves excessive inflammation of nerve cells. The team also argued that
because these proteins tend to be much smaller than most other proteins, they are likely
to be overlooked in large-scale protein studies. The researchers extracted spinal fluid
from two groups of patients. The first group, comprising 41 patients, was known to have
Lou Gehrig's disease, while the second group of 31 patients complained of muscle problems
such as weakness and cramps.

University of Iowa researchers investigating the basic biology of cell signaling have made
a discovery that may have therapeutic implications for amyotrophic lateral sclerosis (ALS)
and other neurodegenerative diseases. The UI team, led by John Engelhardt, Ph.D.,
professor and head of anatomy and cell biology in the UI Roy J. and Lucille A. Carver
College of Medicine, discovered that two cell-signaling proteins called Nox1 and Nox2
appear to play an important role in disease progression of an inherited form of ALS. This
work is published in the Sept. 13 issue of the Journal of Clinical Investigation.Deleting
either Nox1 or Nox2 genes from mice with the inherited type of ALS significantly increased
the lifespan of the mice. Nox2 deletion produces the most dramatic effect, nearly doubling
the lifespan of the mice. In addition, Nox2 deletion dramatically increased the survival
index -- the time from disease onset to death. This is the first report of a single gene
that affects the survival index in ALS models.

The risk of developing a fatal neurodegenerative disease is 25 times higher than the norm
for people who live around Mascoma Lake, according to researchers studying the possibility
of a link between lake bacteria and neurological illness.

Scientists have identified a gene in mice that plays a central role in the proper
development of one of the nerve cells that goes bad in amyotrophic lateral sclerosis, or
Lou Gehrig's disease, and some other diseases that affect our motor neurons.The study is
the result of a collaboration by scientists at the University of Rochester Medical Center
who normally focus on the eye, working together with a developmental neuroscientist at
Harvard who focuses on the cerebral cortex. The work appears in the Oct. 23 issue of the
journal Neuron. The work centers on corticospinal neurons, crucial nerve cells that
connect the brain to the spinal cord. These neurons degenerate in patients with ALS, and
their injury can play a central role in spinal cord injury as well. These are the longest
nerves in the central nervous system  nerves sometimes several feet long that run
from the brain to the spinal cord. As the ends of the nerves degenerate, patients lose the
ability to control their muscles. The team led by Lin Gan, Ph.D., of Rochester and Jeffrey
D. Macklis, M.D., D.HST, of Harvard showed that a protein known as Bhlhb5 is central to
how the brain's progenitor cells ultimately become corticospinal motor neurons, one type
of neuron that deteriorates in ALS. The same group of neurons also degenerates in patients
with a rare neurological disease known as hereditary spastic paraplegia. The work by the
Harvard and Rochester scientists marks an important step in scientists' understanding of
how stem cells in the brain eventually grow into the extraordinary network of circuits
that make up the human nervous system. Understanding how the body determines the destiny
of stem and progenitor cells is crucial if physicians are to ultimately use the cells to
create new treatments for motor neuron diseases like ALS and HSP, as well as other
conditions such as Parkinson's and Huntington's diseases and spinal cord injury. Macklis'
team is a world leader in discovering how the brain determines the destiny of its cells.
The process is a bit like what happens on a construction site, where a foreman taps the
expertise of a variety of workers  carpenters, plumbers, bricklayers, and so on
 as needed to build a given structure. In the brain, teams of molecular signaling
molecules are brought together to create nerve cells out of raw material where and when
needed. Hundreds of such signaling molecules are brought together instantly and
continually to allow the brain to create the nerve cells it needs for growth and
development. "How does the brain take a broad class of neurons and decide which ones
to send to the spinal cord, or which will connect to our visual centers?" said
Macklis, who is director of the Center for Nervous System Repair at Massachusetts General
Hospital and at Harvard.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating
condition in which motor neuron degeneration causes progressive loss of movement and
muscle tone, leading to death. Overcoming the limited success of previous models, a report
published in Disease Models & Mechanisms (DMM), dmm.biologists.org describes how
neurons can be derived from human stem cells, and engineered to mimic inherited ALS.
Researchers at the University of California Los Angeles developed an optimized protocol to
generate motor neurons from human embryonic stem cells (ES cells), which express normal or
mutant forms of the SOD-1 gene, which is linked to inherited, familial ALS. Resulting
cells exhibit hallmark characteristics of motor nerve cells, and neurons expressing mutant
SOD-1 display abnormalities typical of ALS. Defects included shortened cell projections
and a reduced life span compared to cells containing the normal SOD-1 gene. This human
cell-derived model of ALS provides a new method of studying this disease and testing novel
therapeutics. This is especially helpful as only one drug is approved to help slow ALS
progression, and animal models currently used in drug development have had limited
success. Additionally, this research may aid other gene-linked neurodegenerative diseases,
as they too may benefit from studies in a human cell-derived model.

Research that has discovered a new gene whose mutations cause 5 percent of inherited cases
of ALS (amyotrophic lateral sclerosis) is part of a national study led by the Northwestern
University Feinberg School of Medicine. The study reported in Science today (Feb. 27)
points to a common cellular deficiency in the fatal neurological disorder, said Teepu
Siddique, M.D., Les Turner ALS Foundation/Herbert C. Wenske Foundation Professor in the
Davee Department of Neurology and Clinical Neurosciences and Department of Cell and
Molecular Biology and Director of the Division of Neuromuscular Medicine at the Feinberg
School. The new research is part of a national collaboration directed by Siddique, the
principal investigator for the "Genetics of ALS" project funded at Feinberg by
the National Institutes of Health. Earlier research by Siddique and colleagues extended
the genetic knowledge of familial (inherited) ALS by identifying the first and second ALS
genes (the SOD1 gene in 1993 and the ALSIN gene in 2001), in addition to identifying loci
on chromosomes 9, 15, 16, and X. The study published today discovered aFUS/TLS gene
mutations in ALS families collected through efforts of the NIH-funded multi-center project
and included among others a large Italian family previously studied by Siddique and
Cortelli.

A genetic variant that substantially improves survival of individuals with amyotrophic
lateral sclerosis (ALS), also known as Lou Gehrig's disease, has been indentified by a
consortium of researchers led by John Landers, PhD, Associate Professor of Neurology and
Robert Brown, MD, DPhil, Chair and Professor of Neurology at the University of
Massachusetts Medical School. Discovery of the KIFAP3 gene variant is reported in the
Proceedings of the National Academy of Sciences. "This report is the first to
describe genetic factors that determine rate of progression in ALS," said Brown.
"The finding reflects a truly international collaboration in which physicians and
scientists from nearly 20 teams in several countries worked together to use new methods in
genetics to understand ALS." ALS is a progressive, neurodegenerative disorder
affecting the motor neurons in the central nervous system. As motor neurons die, the
brain's ability to send signals to the body's muscles is compromised. This leads to loss
of voluntary muscle movement, paralysis and eventually death from respiratory failure. In
1993, a team of researchers led by Dr. Brown discovered the first gene linked to familial
ALS, a protein anti-oxidant known as superoxide dismutase, or SOD1. Earlier this year, Dr.
Brown and his colleagues discovered a mutation in the FUS/TLS gene which is estimated to
account for 5 percent of inherited ALS cases. There are only four genes known, that when
mutated, cause familial ALS. The KIFAP3 gene variant is the first to be linked with the
rate of progression in ALS. To isolate the KIFAP3 gene variant, a consortium of
researchers from the U.S., Mexico, Israel and Europe examined more than 300,000 genetic
variants in over 1,800 people with ALS and nearly 2,200 unaffected controls. The approach
is based on the assumption that naturally occurring gene variations can influence both
disease susceptibility and the way a disease runs its course once underway. During their
search, the consortium detected a beneficial variant of the KIFAP3 gene which was
associated with an increase in survival time of 40 to 50 percent.

A team of Canadian and French researchers has identified a novel gene responsible for a
significant fraction of ALS (sporadic amyotrophic lateral sclerosis) cases. ALS is
commonly referred to as Lou Gehrigs disease, an incurable neuromuscular disorder
that affects motor neurons and leads to paralysis and death within one to five years.
Published in the current online edition of Nature Genetics, the study on 200 human
subjects with ALS was led by Doctors Guy Rouleau, Edor Kabashi, Paul Valdmanis of the
Research Centre of the Centre hospitalier de l'Université de Montréal (CRCHUM). The team
identified several genetic mutations in the TDP-43 gene by studying ALS patients from
France and Quebec. They established TDP-43 as the gene responsible for up to five percent
of the ALS patients. The breakthrough is the result of teamwork with peers from the
Waterloo and Laval universities in Canada and the Fédération des maladies du système
nerveux and the Institute of Biology (Unité de Neurologie Comportementale et
Dégénérative) in France.

More genes for Lou Gehrig's disease
identified, according to Penn researchers

In recent months a spate of mutations have been found in a disease protein called TDP-43
that is implicated in two neurodegenerative disorders: amyotrophic lateral sclerosis, also
called Lou Gehrigs disease, and certain types of frontotemporal dementia. These
mutations could potentially become candidates for drug targets. Recently, colleagues at
the University of Pennsylvania School of Medicine and Veterans Affairs in Seattle, Wash.
have found two more mutations.

Preliminary results show that a common environmental chemical may increase the risk of
developing amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs disease,
according to research that will be presented at the American Academy of Neurology 60th
Anniversary Annual Meeting in Chicago, April 1219, 2008.

The study was based on the Cancer Prevention Study II of the American Cancer Society. Over
one million people were asked to report their exposure to 12 types of chemicals. The
participants were followed for 15 years, and the number of people who died during that
time of ALS was tracked. A total of 617 men and 539 women died from ALS during the study.

Researchers found no significant link between ALS and exposure to most chemicals,
including pesticides and herbicides. People who reported that they had regular exposure to
formaldehyde, however, were 34 percent more likely to develop ALS than those with no
exposure to formaldehyde.

It explores if a combination of existing
medications and supplements, plus lifestyle and dietary changes may slow the progress of
neurodegeneration in ALS/MND. I was diagnosed with ALS/MND in February 1994 but am now in
remission. I am still walking, talking and looking after myself. My symptoms decreased
significantly and have not worsened in eight years. Why this is the case is explained on
this website. It may be due to my experimentation with antioxidants, diet and lifestyle
changes. Other factors
are almost certainly involved and are also discussed here.

A University of California, Irvine neurologist is part of a national group of scientists
who have identified the active genes in sporadic amyotrophic lateral sclerosis, a
discovery that provides expanded opportunities for developing therapies to treat

Researchers have identified a biochemical switch required for nerve cells to respond to
DNA damage. The finding, scheduled for advance online publication in Nature Cell Biology,
illuminates a connection between proteins involved in neurodegenerative disease and in
cells' response to DNA damage. Most children with the inherited disease ataxia
telangiectasia are wheelchair-bound by age 10 because of neurological problems. Patients
also have weakened immune systems and more frequent leukemias, and are more sensitive to
radiation. The underlying problem comes from mutations in the ATM (ataxia telangiectasia
mutated) gene, which encodes an enzyme that controls cells' response to and repair of DNA
damage. ATM can be turned on experimentally by treating cells with chemicals that damage
DNA. After other proteins in the cell detected broken DNA needing repair, scientists had
thought that the ATM protein could activate itself directly. Emory researchers have shown
that an additional step is necessary first. "In neurons that are not dividing
anymore, we now know that another regulator is involved: Cdk5," says Zixu Mao, MD,
PhD, associate professor of pharmacology and neurology at Emory University School of
Medicine. Working with postdoctoral fellows Bo Tian, PhD and Qian Yang, PhD, Mao found
that the Cdk5 protein must activate ATM before ATM can do its job in neurons. The results
support the idea that Cdk5 may be a potential drug target. Cdk5 contributes to normal
brain development, and aberrant Cdk5 activity is known to be involved in the death of
neurons in several neurodegenerative diseases, including Alzheimer's, Parkinson's and
amyotrophic lateral sclerosis.

An incurable, paralyzing disease in humans is now genetically linked to a similar disease
in dogs. Researchers from the University of Missouri and the Broad Institute have found
that the genetic mutation responsible for degenerative myelopathy (DM) in dogs is the same
mutation that causes amyotrophic lateral sclerosis (ALS), the human disease also known as
Lou Gehrig's Disease. As a result of the discovery, which will be published in the
Proceedings of the National Academy of Sciences this week, researchers can now use dogs
with DM as animal models to help identify therapeutic interventions for curing the human
disease, ALS. "We uncovered the genetic mutation of degenerative myelopathy, which
has been unknown for 30 years, and linked it to ALS, a human disease that has no
cure," said Joan Coates, a veterinary neurologist and associate professor of
veterinary medicine and surgery in the MU College of Veterinary Medicine. "Dogs with
DM are likely to provide scientists with a more reliable animal model for ALS. Also, this
discovery will pave the way for DNA tests that will aid dog breeders in avoiding DM in the
future." Previously, ALS research has relied heavily on transgenic rodents that
expressed the mutant human gene SOD1, which causes ALS. Researchers found that dogs with
DM also had mutations in their SOD1 gene. Many rodent models possess very high levels of
the SOD1 protein that can produce pathologic processes distinct from those occurring in
ALS patients. Since the SOD1 mutation is spontaneous in dogs, the clinical spectrum in
dogs may represent more accurately that of human ALS. "Compared with the rodent
models for ALS, dogs with DM are more similar to people in size, structure and complexity
of their nervous systems, and duration of the disease," said Gary Johnson, associate
professor of veterinary pathobiology in the MU College of Veterinary Medicine. "The
results from clinical trials conducted with DM-affected dogs may better predict the
efficacies of therapeutic interventions for treating ALS in humans."

Amyotrophic lateral sclerosis, more commonly known as Lou Gehrig's disease, is a fatal
neurodegenerative disease caused by the death of motor neurons in the brain and spinal
cord that control muscle movements from walking and swallowing to breathing. In a
groundbreaking study this week in PLoS Biology, Brandeis and Harvard Medical School
scientists report key findings about the cause and occurrence of the familial form of ALS.

Harvard and Columbia scientists have for the first time used a new technique to transform
an ALS patient's skin cells into motor neurons, a process that may be used in the future
to create tailor-made cells to treat the debilitating disease. The research will be
published July 31 in the online version of the journal Science.

Inspired by the use of microarray chips that look for gene combinations, psychologists are
using "pattern array" software to spot movements in rats that might help them
predict diseases such as Lou Gehrig's syndrome.

In what the researchers say could be promising news in the quest to find a therapy to slow
the progression of amyotrophic lateral sclerosis, or Lou Gehrig's disease, scientists at
the University of California, San Diego School of Medicine have shown that targeting
neuronal support cells called astrocytes sharply slows disease progression in mice.

Inspired by the use of microarray chips that look for gene combinations, psychologists are
using "pattern array" software to spot movements in rats that might help them
predict diseases such as Lou Gehrig's syndrome. A report in the August issue of Behavioral
Neuroscience, published by the American Psychological Association, describes how this
novel use of data mining may enable investigators to test therapies to delay or even
prevent disease, starting with hereditary forms.

First trial in patients with a
potential treatment of the incurable ALS muscle disease - Project of VIB, UZ Leuven and
NeuroNova

Permission has been granted to start the first safety and tolerability trial on patients
for a remedy for ALS. ALS is an incurable, paralyzing neurodegenerative disorder that
strikes 5 persons in every 100,000. The disease commonly affects healthy people in the
most active period of their lives - without warning. Researchers from VIB at the
K.U.Leuven have previously shown the possibilities for the use of VEGF in the treatment of
ALS through work in animal models. The Swedish Biopharmaceutical company NeuroNova has
already built upon this research. Together with UZ Leuven theyll start the first
evaluation of safety and tolerability of the drug in patients by the end of this year.
This is an important step in the development of a new treatment. It will take several
years before the protein can be made available as a medicine.

Long thought of as mere bystanders, astrocytes are crucial for the survival and well-being
of motor neurons, which control voluntary muscle movements. In fact, defective astrocytes
can lay waste to motor neurons and are the main suspects in the muscle-wasting disease
amyotrophic lateral sclerosis (ALS). To get to the root of this complicated relationship,
researchers from the Salk Institute for Biological Studies for the very first time
established a human embryonic stem cell (hESC)-based system for modeling ALS. Their study
confirmed that dysfunctional human astrocytes turn against their charges and kill off
healthy motor neurons. But more importantly, treating the cultured cells with apocynin, a
powerful anti-oxidant, staved off motor neuron death caused by malfunctioning
astrocytes.Their findings, which appear in the Dec. 4 issue of the journal Cell Stem Cell,
provide new insight into the toxic pathways that contribute to the demise of motor neurons
in ALS and open up new possibilities for drug-screening experiments using human ALS in
vitro models, as well as clinical interventions using astrocyte-based cell therapies.
"A variety of drugs that had demonstrated significant efficacy in mouse models didn't
keep their promise in both preclinical and clinical trials," says Fred H. Gage,
Ph.D., a professor in the Laboratory for Genetics, who led the study. In fact, just one
drugriluzole has been approved by the FDA to treat ALS, and it only slows the
course of the disease by two months. "There is an urgent need for new ALS models that
have the potential to translate into clinical trials and that could, at a minimum, be used
in conjunction with the murine models to verify drugs and drug targets," says Gage.